Nine years after his "Eureka! moment," John Kopchick's invention has taken the form of a drug that one day may be used to treat such diseases as gigantism, acromegaly, diabe
tic eye and kidney disease, and some forms of cancer.

Photo: Rick Fatica

By Kelli Whitlock

The path to discovery is rarely obvious and hardly ever glamorous. A key, a kite and a wayward bolt of lightning helped identify electrical currents. Moldy bread led to penicillin. A falling apple explained gravity.

Still, an invention is a thing of wonder. We marvel at the
creation of the transistor, welcome the identification of genes that cause
disease and are in awe at the speed of a Pentium processor. If the
inventive process itself is sometimes fortuitous, it only adds to the
mystique.

For researchers in the lab of Ohio University's John Kopchick, the
route was marked by tiny mice that were supposed to be big. In the late
1980s, Kopchick's group set out to study growth hormone, a product of the
pituitary gland involved in many bodily processes. But
like many creators
before them, they soon became accidental tourists on the road to
discovery.

"Sometimes in science, what you're looking for isn't exactly what you
find," says Kopchick, Goll-Ohio professor of molecular biology. The
researchers weren't looking for a protein antagonist in their studies at
Ohio University's Edison Biotechnology Institute. But that's what they found. The invention, a manipulation of one amino acid in a growth hormone
protein chain, inhibits the action of
the hormone at the cellular level.

Nine years after Kopchick and co-inventor Wen Chen, a senior
scientist at EBI, experienced their "Eureka! moment," their discovery has
become the basis of a drug that one day may be used to treat diseases
characterized by an overproduction of growth hormone, including gigantism,
acromegaly, diabetic eye and kidney disease, and some forms of cancer. The
drug, called TrovertŪ, has been developed by Sensus Drug Development Corp.,
a pharmaceutical firm in A
ustin, Texas, started by Ohio University alumnus
Richard Hawkins, BS '72.

Sensus is conducting clinical trials of the drug for use in some
40,000 people worldwide with acromegaly, a disease caused by a brain tumor
that affects pituitary gland cells. People with acromegaly have elevated
growth hormone levels; display abnormal growth of the hands, feet, and
bone and cartilage in the face and other parts of the body; and
enlargement of the liver, spleen, kidneys and heart. Phase III human
clinical trials are under way at nine sites in the United States and Europe. If all goes well, TrovertŪ could be up for Food and Drug
Administration approval for the treatment of acromegaly by the end of
1999.

Meanwhile, studies by Kopchick's research team suggest diabetic
mice transgenically altered to express the growth hormone antagonists do
not develop diabetes-related eye or kidney disease. The studies were
convincing enough to send TrovertŪ to human clinical trials for diabetic
eye
disease, the leading cause of blindness in the U.S. Results from Phase
II human trials now being conducted at four sites are expected next
spring. Phase II human trials for the treatment of diabetic kidney disease
could begin next spring as well.

"We're really proud that our research could actually help people
with a variety of disease states," says Kopchick, who with Chen was
credited at an Ohio University ceremony this fall for developing the
Invention of the Year.

Until
20 years ago, universities weren't allowed to own their
inventions. The 1980 Bayh-Dole Act, sponsored by former Sens. Birch Bayh and Robert Dole, enabled universities, nonprofit research institutions and
small businesses to own and patent inventions developed under federally
funded research programs. Since its passage, the number of patents granted
for university inventions has risen from about 250 to 1,500 a year,
according to the Association of University Technology Managers. The group
also reports
that the licensing of university inventions -- called
technology transfer -- adds more than $21 billion to the economy and
supports 180,000 jobs annually.

Ohio University has received 34 U.S. patents since 1973 and $1.6
million in revenue from licensing agreements. Technology developed on
campus has led to the creation of five new companies, three of which got
their start in the university's Innovation Center. (See Related Story). A 1996 survey by the As
sociation of University and Technology
Managers ranked the university among the top 50 in the nation for
technology transfer, a listing based on business start-ups attributed to
university-created technology, licenses executed, new patents applied for,
research funding related to a license, total industrial funding and licensing income.

"Moving something from the lab to the marketplace is a huge step,"
says Gary Meyer, assistant vice president for economic and technology
development and
director of Ohio University's Technology Transfer Office.

The venture begins with a marketable idea, such as a protein
antagonist with implications for drug development. Patent protection of
the invention, also called intellectual property, is a critical part of
the process. The university, Kopchick and Chen received the first patent
for growth hormone antagonists in 1994 and a second in 1997. More patents
are pending.

Once domestic and foreign patent applications have been
filed, the
intellectual property rights are established and the search begins for a
commercial partner. In Kopchick's case, that search resulted in a
partnership with Sensus' Hawkins, a Baltimore, Ohio, native who began a
career in the pharmaceutical industry after earning a degree in secondary
education with a focus on biology.

"The wisdom of leaders in Ohio and at the university who developed the Edison Biotechnology Institute and attracted such capable researchers
to run it is impress
ive," Hawkins says. "It's all a part of the growing-up
process of any university."

Other university faculty are learning to negotiate the technology
transfer process, among them Marcia Kieliszewski, an assistant professor
of chemistry and inventor of a designer gene that could pique the interest
of soft drink manufacturers. A component of many soft drinks is gum
arabic, which is found in trees in Sudan. The Sudanese cut the bark of the
trees, prompting the production of gum arabic, a thi
ck, sticky gum that
plugs the trees' wounds. The gum arabic is harvested, processed and sold to
companies that use it in confections, soft drinks and other products. A
trading ban with Sudan presents a problem for industry and an opportunity
for Kieliszewski.

"The important part of gum arabic is glycoprotein, a protein that's
covered with sugar, Kieliszewski says. "We identified the protein sequence
of that glycoprotein and used it to design our own gene, one that could be
made to work
in plants commonly found here, such as tomato plants or tobacco plants."

It could take two to five years for Kieliszewski to receive the
domestic and foreign patents she has applied for in the past year.
Meanwhile, she continues her work safe in the knowledge that her
intellectual property is protected.

Faculty inventors on campus are at different stages of the
technology transfer process. Some are completing the necessary paperwork
to obtain patent protection, while others,
like Kieliszewski, are awaiting
word on their patent applications. Several are in collaboration with
industry partners on their way to taking Ohio University technology to the
public. Still more technologies are awaiting a match with a commercial
partner: Inventions designed to do everything from control zebra mussels
in water systems to recycle plastic materials in a new way are available
for licensing.

Technology transfer is a burgeoning area at Ohio University and on
campuses across
the nation: A survey of technology transfer at national
universities from 1991 to 1995 by the Association of University Technology Managers found a 120 percent increase in U.S. patent applications and a 68
percent rise in licensing activity during that time. That, the group says,
is a sign technology transfer in higher education will continue to grow
into the next decade.

Kopchick agrees such growth is assured. Higher education promotes
the creative exploration of why things are; creativ
ity leads to invention.
If necessity is the mother of invention, curiosity is a next-of-kin.
Kopchick got started in his line of work because he was curious about a
specific biological process. In his case, the wonder of living organisms
and how they grow laid out a rather circuitous path that led to a patented
invention carrying his name and that of Ohio University. But as with all
discoveries supported by technology transfer, the benefits belong to
everyone.

<
td>THE SEQUENCE OF PROGRESS

1989: Researchers in John Kopchick's lab take their first step toward discovery when they manipulate the structure of the growth hormone protein chain. This allowed the scientists to inhibit growth in mice.

1994: Kopchick, Wen Chen and Ohio University receive the first U.S. patent on growth hormone antagonist. A second patent is issued in 1997 and more are pending.

1998: A drug based on their discovery is in human clinical trials for the treatment of acromegaly and diabetic eye disease. While they await results, the group returns to the drawing board to find more uses for the technology.

Kelli Whitlock is the research communications editor and a science writer
for University News Services and Periodicals.